title: An evaluation of the impact of technical bias on the concordance rate between primary and recurrent tumors in breast cancer.
abstract: OBJECTIVE
  Whether or not to biopsy the metastasis in recurrent breast cancer has become mired in controversy. Several studies have shown an important discordance of the immunohistochemical (IHC) determinations for ER, PR and HER2 between primary (PT) and recurrent tumors (RT). Yet it remains unknown within this what impact technical issues have. The aim of our study was to assess whether technical variability might have an impact on the concordance between PT and RT.
  
  
  METHODS
  IHC determinations in paired biopsies from PT and RT were compared under routine vs study conditions. In the former, pathological analysis reproduced the conditions used in the routine of a University Pathology Department. In the latter, in a technical bias-minimizing manner, samples were re-assessed at the same timing and by two independent observers.
  
  
  RESULTS
  128 paired biopsies from 64 patients were analyzed under both conditions. Concordance under routine vs study conditions for ER was 66% vs 93.4% (p = 0.001), for PR 58.7% vs 80.3% (p = 0.064) and for HER2 86.8% vs 96.8% (p = 0.25). Kappa index under routine versus study conditions for ER was 0.27 vs 0.79 (p = 0.002), for PR 0.26 vs 0.39 (p = 0.47) and for HER2 0.67 vs 0.9 (p = 0.14).
  
  
  CONCLUSIONS
  Although discordance rate between PT and RT decreased under conditions minimizing technical issues, some discordant cases appeared not to be subjected to this confounding factor. Either for clinical practice or for future studies reassessment of PT in recurrent breast cancer should be encouraged.
authors.affiliation: Department of Oncology and Hematology, Research Institute INCLIVA, Hospital Clinico Universitario Valencia (HCUV), Avda Blasco Ibañez 17, 46010 Valencia, Spain. Electronic address: japfidalgo@msn.com.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Pérez-Fidalgo
authors.forename: Pilar
authors.initials: P
authors.lastname: Eroles
authors.forename: Jaime
authors.initials: J
authors.lastname: Ferrer
authors.forename: Ana
authors.initials: A
authors.lastname: Bosch
authors.forename: Octavio
authors.initials: O
authors.lastname: Burgués
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez
authors.forename: Begoña
authors.initials: B
authors.lastname: Bermejo
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Ana M
authors.initials: AM
authors.lastname: González-Angulo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000737:chemistry / Q000556:secondary; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D012189:Retrospective Studies
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Estrogen receptor; HER2; Metastatic breast cancer; Progesterone receptor; Technical bias